The objectives of the contract involve the establishment of procedures for the preparation and characterization of live, attenuated, cold- adapted (ca) influenza A and B virus reassortants for use as vaccines. Under the direction of the Project Officer, this laboratory will be a repository for clinical samples from primary field isolates and will evaluate them for potential use as hemagglutinin and neuraminadase donors for the vaccine strains. The Contractor will be responsible for the management, retrieval, analysis, validation and publication of data and the cataloguing, storage, and shipment of the wild-type and reassortant influenza A and B viruses required for the studies. Using a ferret model, the reassortant clones will be characterized as to phenotypic and genotypic stability, virulence, and reactogenicity including the determination of the appropriate dose and schedule for intranasal administration of trivalent ca reassortant vaccines. In addition, the Contractor will supply vaccine clones for distribution to other investigators as requested by the Project Officer and will characterize virus isolated from subjects in clinical tests. Molecular analyses will be conducted in order to further characterize the ca parent viruses and compare them to their wild-type progenitors. Investigations will continue into the mechanisms by which certain of the reassortant vaccine strains become reactogenic in an attempt to better predict the behavior of the vaccine strains in humans.